Trajectories of Plasma Epstein-Barr Virus DNA and Clinical Outcomes in Recurrent or Metastatic Nasopharyngeal Carcinoma Treated With PD-L1 Inhibitors: A Post-Hoc Analysis of a Multicenter, Phase II Study.

Abstract

Background: Reliable biomarkers for predicting clinical outcomes in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) treated with immunotherapy remain limited. This study evaluated the association between longitudinal EBV DNA trajectories and clinical outcomes in patients with R/M NPC receiving immune checkpoint inhibitors.

Methods: This post hoc analysis used data from a multicenter, single-arm, Phase II trial evaluating the programmed cell death-ligand 1 (PD-L1) inhibitor KL-A167 in patients with previously treated R/M NPC. Plasma EBV DNA was measured at baseline and at each scheduled efficacy assessment, which was conducted every six weeks until disease progression. EBV DNA trajectories were distinguished through a logistic trajectory model. Multivariable Cox models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for survival outcomes.

Results: We identified three distinct trajectories: persistently undetectable (n = 17, 13.8%), fluctuating (n = 40, 32.5%), and persistently detectable (n = 66, 53.7%). Compared with the persistently undetectable group, HRs of death were 4.96 (95% CI, 1.60-15.40) and 12.59 (95% CI, 4.01-39.51) for the fluctuating and persistently detectable groups, respectively. HRs of disease progression were 1.96 (95% CI, 0.97-3.96) and 3.22 (95% CI, 1.56-6.67), respectively.

Conclusion: This study suggests that plasma EBV DNA trajectories could be a promising biomarker for monitoring treatment response and longitudinal risk stratification.